THE CELL CYCLE AND CANCER

Control of the Cell cycle

Cell division and cancer Which karyotype is the bladder cancer cell?

This representative karyotype from a human prostate cancer cell line before injection into nude mice shows all human chromosomes with characteristic marker chromosomes

OK…what tells a cell when to divide (or, indeed, when NOT to divide)?

Cell cycle controls

Cell Cycle Control Leland Hartwell Isolated > 100 genes (in yeast cells) directly involved in control of the cell cycle (CDC genes) Introduced the concept of ‘Checkpoints’: where the cell cycle stops to check if DNA has been perfectly duplicated, cell size is correct, etc etc…

Cell cycle control Sir Paul Nurse Used another yeast cell (Saccharomyces) to identify the CDC2 gene (and subsequently the equivalent gene in humans, CDK1), which was THE rate-limiting step controlling onset of S, transition from G1 to S and from G2 to M phase of the cell cycle

Cell Cycle Control Tim Hunt Used sea urchins to identify control proteins which were formed and degraded throughout the cell cycle (cyclins) and bind with CDK molecules, regulating CDK activity and selecting proteins to be phosphorylated

OK…what tells a cell when to divide (or, indeed, when NOT to divide)? Let's get some help from the NOBEL organisation... and how about some help from Harvard? Animation

What’s the link between control of the cell cycle and cancer? In cancer, parts of chromosomes are lost, rearranged or unequally distributed between daughter cells This is often due to defective cell cycle control Genes for CDK and cyclins can function as oncogenes Increased levels of CDK and cyclins are often identified in human cancer cells (e.g. skin, breast)

‘Faulty’ cell division: defective telomeres A telomere is the end of a chromosome. Telomeres are made of repetitive sequences of non-coding DNA that protect the chromosome from damage. Each time a cell divides, the telomeres become shorter. Eventually, the telomeres become so short that the cell can no longer divide.

‘Faulty’ cell division: oncogenes An oncogene is a mutated gene that contributes to the development of a cancer. In their normal, unmutated state, oncogenes are called proto-oncogenes, and they play roles in the regulation of cell division

Great links on cancer biology Cold Harbour website Howard Hughes p53 site

School Trip

School Trip Swiss Oncology Research Institute